Dr. Leonard Mermel, DO, Medical Director of the Department of Epidemiology and Infection Control at Rhode Island Hospital with academic appointment at The Warren Alpert Medical School of Brown University, along with research colleagues; Stephanie L. Angione, Anubhav Tripathi of the Center for Biomedical Engineering at Brown University, Aleksey Novikov, MD, and Jennifer Fieber of Brown University, and Aartik A. Sarma of Harvard Medical School.
Here’s the latest from the Clostridium difficile research community:
The 19.8kb Pathogenicity Locus or PaLoc of C.difficile expresses genes for the toxins as well as genes that regulate toxin production. Additionally mobile genetic elements are also responsible for acquisition of antibiotic resistance genes. Dingle et al. look at the evolutionary history of the mobile elements in C.difficile and suggest that PaLoc is mobilized rarely via homologous recombination, whereas Tn6218 is mobilized frequently through transposition.
Toxin regulation may also be controlled by additional genes other than the usual suspects present on the PaLoc such as flagella. In B. subtilis, the sigma factor SigD controls flagellar synthesis, motility, therefore it is possible that a homolog of SigD present in the C.difficile 630 genome could also control toxin production. A sigD mutant in C. difficile 630 ∆erm displayed decreased expression of genes involved in flagellar biosynthesis, and also of genes encoding TcdA and TcdB as well as TcdR, the positive regulator of the toxins. Thus, SigD appears to be the first positive regulator of the toxin synthesis via direct control of tcdR transcription in C. difficile
C. difficile is present in 60-70% of newborns and infants. It has been speculated that newborns and infants lack the receptors for the disease-causing toxins secreted by C.difficile, and hence, are colonized, but remain disease-free. Alderbeth et al looked at the long term persistence of C.difficile in healthy infants from birth to ≥12 months of age. Carriage of toxin producing genes was also characterized. Most strains (71%) were toxin producers, and 51% belonged to the 001 or 014 ribotypes, which often cause disease in adults. Toxin-producing strains colonizing young children for long time periods may represent a reservoir for strains causing disease in adults.
With the emergence of a hypervirulent strain of C. difficile (BI/NAP1/027), the epidemiology of C. difficile infection has rapidly changed in the last decade. In addition to toxin A and toxin B, hypervirulent strains produce a third toxin, binary toxin. Although it has been speculated that binary toxin has an additive effect to damage already caused by the other two toxins, Kuehne et al created knock out combinations of isogenic toxin mutants of R20291 and assessed their virulence in hamsters. They reconfirm their previous findings where they show either toxin A or toxin B alone can cause fulminant disease in the hamster infection model. In addition they show that in a double toxin mutant (A−B−C+; ie, an isogenic mutant producing only CDT), 3 of 9 animals succumbed to disease, although symptoms vary from those typically associated with C.difficile infection. Signs of wet tail, hemorrhage and inflammation in their small intestines were observed, thus suggesting an independent role of CDT in causing disease.
For the first time the emergence of a hypervirulent strain of C. difficile (BI/NAP1/027) has been reported in China.
Type IV pili are non-covalently assembled appendages, characterized now in both Gram-negative and Gram-positive bacteria. Peipenbrink et al show that C. difficile produces Type IV pili containing PilJ, a pilin with a novel dual-pilin fold. According to the suggested model, the C-terminal pilin domain is exposed in pili, providing a unique interaction surface. The novel fold of PilJ suggests a new mode for Type IV pilus function.
Fecal microbiota transplantation (FMT) has been suggested as a new treatment to manage Clostridium difficile infection (CDI). Lofgren et al use a mathematical model of C. difficile within an intensive care unit (ICU), to examine the potential impact of routine FMT. Results of this study suggest that the routine use of FMT represents a promising approach to reduce complex recurrent cases, but a reduction in CDI incidence will require the use of other methods to prevent transmission.